Central nervous system germinoma – reflecting on insights and considering important next steps

Germinomas as well as non-germinomatous germ cell tumors (NGGCTs) are rare malignant central nervous system tumors predominantly affecting children, adolescents, and young adults. Treatment of germinomas vary significantly worldwide, highlighting the need for a comprehensive strategy to optimize outcomes across all age groups. Incorporating platinum-based chemotherapy into treatment backbones in the 1980s has allowed significant reductions in radiation therapy (RT) volume and dose while maintaining excellent outcomes. This combined-modality approach is primarily utilized in pediatric institutions. Conversely, young adults treated outside pediatric cooperative frameworks often receive an irradiation-only approach, necessitating higher doses and larger volumes. This difference in the use of RT-only versus combined-modality approaches contributes to avoidable long-term toxicities and significantly impacts the well-being of germinoma survivors. Despite substantial progress in reducing RT exposure, the minimal effective dose and optimal target volume required to ensure durable cure while maintaining quality of life and enabling social reintegration remain undetermined. The ACNS2321 study of the Children’s Oncology Group (NCT06368817) and the planned study CNS GCT III from the International Society of Pediatric Oncology (SIOP) present an opportunity to review existing data, identify knowledge gaps, and guide the development of innovative and effective treatment strategies for future international trials. Both studies seek to address unresolved questions in germinoma treatment, including determining the optimal RT dose and volume, refining strategies for managing metastatic and atypically located germinomas, and integrating innovative translational objectives. The goal is to identify curative treatment regimens for germinomas that minimize long-term treatment-related morbidity while maximizing functional recovery and quality of life for all patients. This necessitates global collaborative efforts among both pediatric and adult neuro-oncology networks to standardize treatment protocols, reduce practice variability and rapidly translate emerging research findings into clinical practice. By focusing on both the immediate and long-term needs of patients, the international community can move closer to establishing an optimized age-spanning standard of care for this rare but impactful disease.